Stem cell therapy for

traumatic spinal cord injury

Alicia Fuhrman, MDNorthwest Regional SCI System Forum

University of WashingtonMarch 28, 2018

Disclosures

None

Objectives

• Learn: types of stem cell therapy (SCT)

for SCI

• Understand: state of research about

effectiveness of SCT for SCI

• Apply and Evaluate: safety, risks, and

potential benefits of participating in a

stem cell therapy, clinic, or study

Outline

1.Background and types of stem cells

2.Review of current study results

3.Ethics of stem cell therapy and questions

for future studies

1.Background and types of stem cells

Why stem cells?

• Ability to become any type of cell (almost)

• Readily available from multiple sources

• If autologous (from self), low risk of rejection

Stem cells: a primer

Where do stem cells come from?

• Autologous – from self• Allogenic – from other people

Totipotent zygote stem cell pluripotent embryonic stem cell

ENDODERM MESODERM ECTODERM

Intestine, lungs, glands Skin, nervous systemMesenchymal SC

(stromal cells)

Bone, cartilage, muscle,

marrow, adipose

Hematopoetic SC

Blood

Induced pluripotent (iPSCs)

Multipotent

Pluripotent

Potencyas it relates to

stem cells

TotipotentZygote

Embryonic

Can become

anything

Can become

most

things

Can become

some things

Adult stem cells

Umbilical cord

Types of cells used in reviewed studies

Neural stem/progenitor cells(precursor brain cells)

1. SCI epidemiology and types of stem cells

2. Review of current study results

3. Ethics of stem cell therapy and questions for

future studies

Outline

Search through medical literature

Filter: Humans, English 329 articles identified

through primary search

39 articles in final

analysis

294 articles excluded

for nonhuman studies, not in English, errors in

classification

4 articles identified

from references of primary search

978 patients

total

Not every search result is a good one

Read and analyzed

Variables

▪ Timing after injury

▪ Completeness▪ Type of cells

▪ Dose of cells ▪ Route of administration

Who were in these studies?

▪ Mix of patients with chronic and acute injuries,

paraplegia and tetraplegia, complete and incomplete▪ Majority of patients had chronic injuries, mix of

paraplegia or tetraplegia, and were complete

Cell Types

The majority of studies in this review assessed the

effects of autologous MSCs as treatment for SCI.

From self

Totipotent zygote stem cell pluripotent embryonic stem cell

ENDODERM MESODERM ECTODERM

Intestine, lungs, glands Skin, nervous systemMesenchymal SC

(stromal cells)

Bone, cartilage, muscle,

marrow, adipose

Hematopoetic SC

Blood

Stem cell therapy: did it help?

39 studies

26 documented AIS

18 8Benefit No benefit

Change in AIS (ASIA) classification (A-E)

It helped! What’s the problem?

• These studies were all very different

• different injury levels, completeness, time since injury,

cells used, number in study, non-randomized, non-blind

• Although these were in “peer-reviewed” journals,

overall they are not very “strong” studies

“[Of those with neurologically complete injuries at 1

year], 3.5% improved to AIS B, and up to 1.05% each

improved to AIS grades C and D at 5 years post injury”

Initial

AIS grade

AIS Grade at Discharge (%) AIS Grade at 1 Year (%)

A B C D A B C D

A 80.2 13.1 6.2 0.5 72.2 10.7 13.9 3.2

B 5.0 53.4 33.9 7.7 10.7 35.7 32.2 21.4

C 1.8 2.0 44.3 51.9 1.8 6.4 19.3 72.5

D 0.4 0 0.6 99.0 0 0 0 100

Park 2012

Korean study that used autologous MSCs into the spinal cord or spinal

space (via spinal tap):

• Patient 1 (8 months from injury) started at less than antigravity

strength in elbow flexors/extensors and wrist extensors and

returned to near-full strength in those muscles at 40 months post-

treatment

• Patient 2 (38 months from injury) started at antigravity strength in

elbow extensors and regained full strength in those muscles at 39

months post-treatment

• Patient 3 (96 months post injury) started at flicker to near-anti-

gravity strength in finger muscles and regained full strength in

those muscles at 30 months post-treatment

Study example of ”success”

Expected functional outcomes

Spinal Cord Injury CPG 1999

FIM Score Ability

7 Independent

6 Independent with assistive device

5 Superv ision

4 Minimal assistance

3 Moderate assistance

2 Maximal assistance

1 Total assistance Spinal Cord Injury CPG 1999

An adverse event or suspected adverse reaction is

considered “serious” if […] it results in any of the

following outcomes: Death, a life-threatening adverse

event, inpatient hospitalization or prolongation of

existing hospitalization, a persistent or significant

incapacity or substantial disruption of the ability to

conduct normal life functions, or a congenital

anomaly/birth defect.

US FDA Code of Federal Regulations

Dr. Geeta Shroff

Risks• 18 year old woman

at time of injury

• 3 years later

underwent olfactory

(nasal cell) transplant

• 8 years later had

back pain

What is this?

Dlouhy 2014

Why aren’t there more stem cell trials for SCI?

January 11, 2018

• Lack of standardization (type of stem cell, dose, route)

• Difficult to randomize and/or control, small study sizes

• FDA approval (usually lacking or slow)

• Expensive (cost of treatment, travel, sick time)

• Unclear level of risk

Outline

1.SCI epidemiology and types of stem cells

2.Review of current study results

3.Ethics of stem cell therapy and questions

for future studies

What’s ethics got to do with it?

Saito 2008

Excerpt from one paper…

Medical Vulnerability

“Social groups who have an increased relative risk or

susceptibility to adverse health outcomes.”

Flaskerud 1998

Balance in reporting: is it #fakenews?

On SCI Advocacy websites thatmentioned stem cells…

Positive:negative statements

Parke 2010

Ethics-related information

comprised 20% of total content

10:1

Robillard 2015

Most SCI tweets pertaining to stem cell therapy

neutral or positive

Risks of social media

Kwon 2012

Minimum chance of functional recovery

required for entering a SCT research trial

“What would you want your chances to be for getting

some functional recovery back?”

Risk-taking

Kwon 2012

▪ Majority of stem cell therapy information is neutral or

positive, both on websites and social media▪ Majority of respondents (8 of 10) would be satisfied with

1-50% chance of functional recovery from SCT▪ Up to 25% of respondents willing to participate in SCT

regardless of risk

The literature supports that:

Questions when reviewing future studies

Snyder 2012

Were assessments performed in a blindedmanner?

Were participants followed and observed for at least 4 months after the treatment?

Are the results reproducible?

From the Christopher and Dana Reeve Foundation

From the Christopher and Dana Reeve Foundation

From the Christopher and Dana Reeve Foundation

On the horizon…

Hospital Sao Rafael – autologous MSCsFerrer – allogenic MSCs Sun Yat Sen – umbilical MSCsBeijing – MSCs or NSCs on collagen scaffoldMiami – autologous SchwannDa Nang – autologous mononuclearSci star – oligodendrocyte progenitorUCSD – neural stemBioArctic – FGF1 and peripheral nerve

Excerpted from SCOPE 2017

Non-SCT

Excerpted from SCOPE 2017

SPRING trial VX-201/Cethrin

Eusol rFGF

Rick Hansen Minocycline

RISCIS Riluzole

Kringle Hepatocyte GF

OSU Glyburide

Kessler Dalfampyridine

Others Hypothermia, HBO, AIH, BP

I’m interested in learning more… what do I do next?

Closerlookatstemcells.org

How do I learn more about clinical trials?

Take-home points

• Stem cell therapy for spinal cord injury has shown

some benefit, but is not without risks of its own; additionally, “benefits” are not guaranteed

• If you are considering stem cell therapy: Do your homework!

• Beware of anecdotal evidence or testimonials

• If it sounds too good to be true, it probably is

Acknowledgements

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